The effects of different endocrine disruptors defining compound-specific alterations of gene expression profiles in the developing testis

Pedro P. López-Casas^a^,¹^,²,
Sefika C. Mizrak^b^,^c^,²,
Luis A. López-Fernández^d,
María Paz^a,
Dirk G. de Rooij^b^,^c,
Jesús del Mazo^a^,^,

^a Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), Ramiro de Maeztu 9, 28040 Madrid, Spain
^b Department of Endocrinology and Metabolism, Faculty of Science, Utrecht University, Utrecht, The Netherlands
^c Department of Reproductive Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
^d Hospital General Universitario Gregorio Marañón, Doctor Esquerdo 46, 28007 Madrid, Spain

Received 4 March 2011. Revised 20 December 2011. Accepted 24 December 2011. Available online 5 January 2012.

http://dx.doi.org/10.1016/j.reprotox.2011.12.012, How to Cite or Link Using DOI
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Abstract

Environmental contaminants considered endocrine disruptors have been shown to affect testis development and function but the mechanisms of action are not clear. We now have analyzed the effects on the transcriptome in testes of mice exposed to mono-(2-ethylhexyl)-phthalate (9.2; 46.3 or 92.7 mg/kg/d), zearalenone (1.3; 3.9 or 6.6 mg/kg/d), lindane (16.6; 32.2 or 64.4 mg/kg/d), bisphenol-A (0.16; 16 or 64 mg/kg/d) or 17β-estradiol (0.006; 0.012 or 0.048 mg/kg/d). The compounds were orally administered in the drinking water during distinct developmental periods: (A) mothers were exposed only during the two weeks before mating; (B) the exposure was continued during pregnancy until birth or (C) exposure was continued for a further four weeks after birth. Testes were studied at four weeks of age. Mono-(2-ethylhexyl)-phthalate and zearalenone, both produced specific alterations of gene signatures. Interestingly, this was irrespective of the concentration of the toxicant or the developmental period during which exposure occurred.

Highlights

► Endocrine disruptors (EDs) adversely affect the health of organisms or their progeny including their reproductive systems. ► We have analyzed the effects on the transcriptome in testes of mice exposed to phthalate, zearalenone, lindane, BPA or E2. ► Mono-(2-ethylhexyl)-phthalate and zearalenone, both produced specific alterations of gene signatures in developing testis. ► The effect of both EDs was irrespective of the concentration or the developmental period during which exposure occurred. ► This analysis strongly suggests that EDs can cause developmental reprogramming of gene expression during testis development.